The LINKS motif zippers trans-acyltransferase polyketide synthase assembly lines into a biosynthetic megacomplex

Gay, Darren C.; Wagner, Drew T.; Meinke, Jessica L.; Zogzas, Charles E.; Gay, Glen R.; Keatinge-Clay, Adrian T.

doi:10.1016/j.jsb.2015.12.011

Title: The LINKS motif zippers trans-acyltransferase polyketide synthase assembly lines into a biosynthetic megacomplex

Journal Article · Wed Dec 23 00:00:00 EST 2015 · Journal of Structural Biology

DOI:https://doi.org/10.1016/j.jsb.2015.12.011· OSTI ID:1357643

Gay, Darren C. ^[1]; Wagner, Drew T. ^[1]; Meinke, Jessica L. ^[1]; Zogzas, Charles E. ^[1]; Gay, Glen R. ^[1]; Keatinge-Clay, Adrian T. ^[1]

Univ. of Texas, Austin, TX (United States)

Polyketides such as the clinically-valuable antibacterial agent mupirocin are constructed by architecturally-sophisticated assembly lines known as trans-acyltransferase polyketide synthases. Organelle-sized megacomplexes composed of several copies of trans-acyltransferase polyketide synthase assembly lines have been observed by others through transmission electron microscopy to be located at the Bacillus subtilis plasma membrane, where the synthesis and export of the antibacterial polyketide bacillaene takes place. In this work we analyze ten crystal structures of trans-acyltransferase polyketide synthases ketosynthase domains, seven of which are reported here for the first time, to characterize a motif capable of zippering assembly lines into a megacomplex. While each of the three-helix LINKS (Laterally-INteracting Ketosynthase Sequence) motifs is observed to similarly dock with a spatially-reversed copy of itself through hydrophobic and ionic interactions, the amino acid sequences of this motif are not conserved. Such a code is appropriate for mediating homotypic contacts between assembly lines to ensure the ordered self-assembly of a noncovalent, yet tightly-knit, enzymatic network. Furthermore, LINKS-mediated lateral interactions would also have the effect of bolstering the vertical association of the polypeptides that comprise a polyketide synthase assembly line.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; National Institutes of Health (NIH); Welch Foundation

Grant/Contract Number:: AC02-05CH11231; AC02-06CH11357; GM106112; F-1712

OSTI ID:: 1357643

Alternate ID(s):: OSTI ID: 1400020

Journal Information:: Journal of Structural Biology, Vol. 193, Issue 3; ISSN 1047-8477

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 17 works

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59 BASIC BIOLOGICAL SCIENCES
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Title: The LINKS motif zippers trans-acyltransferase polyketide synthase assembly lines into a biosynthetic megacomplex

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